PROJECT SUMMARY/ABSTRACT Although many evidence-based interventions have been identified to address the consequences of the opioid epidemic in the United States, much less progress has made been toward preventing the initiation of opioid misuse and the development of opioid use disorder (OUD). Recognizing the urgent need to fill this gap in knowledge, the National Institute on Drug Abuse (NIDA) is launching the HEAL Preventing Opioid Misuse and Opioid Use Disorder in Older Adolescents and Young Adults Initiative. Ten research projects (RPs), one coordinating center (CC), the steering committee (SC), and NIDA and other federal staff will collaborate to evaluate evidence-based prevention and intervention services for older adolescents and young adults across diverse settings and populations. We recognize that this important and complex endeavor requires exceptional coordination across a range of activities inherent to multi-site consortia. We propose a CC to facilitate cross-site activities and provide centralized support for the HEAL Prevention Collaborative (HPC). Our CC has five Specific Aims. We will provide centralized operational, administrative, and logistical infrastructure to facilitate consortium coordination and communication (Aim 1). We will provide implementation science expertise to understand the delivery and adaptation of evidence- based interventions within different programmatic settings (Aim 2). We will establish an infrastructure for cross-site data collection, management, harmonization, and data sharing (Aim 3). We will provide expert methodological and statistical consultation (Aim 4). We will conduct rigorous economic evaluation to guide decisionmakers in choosing prevention strategies that produce the greatest impact (Aim 5). Our CC team is led by multiple Principal Investigators?Drs. Phillip Graham and Kevin Conway?who are experienced leaders of multi-site studies and experts in consensus building, data harmonization, program evaluation, and addiction etiology. The broader team of Core leaders, key staff, and consultants brings robust scientific and implementation science skills interwoven with a deep understanding of the opioid crisis, prevention science, and the economics of opioid misuse and addiction. We offer proven computational infrastructure and statistical expertise to support all the required data management and analysis needs for the consortium. We are backed by RTI's unsurpassed experience and proficiency?born from successful leadership of over 40 other CCs?to ensure that we support and accomplish the aims. Collectively, we are well-prepared to apply prevention science concepts to the Nation's approach to the opioid crisis.